Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13996 | 42211;42212;42213 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| N2AB | 12355 | 37288;37289;37290 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| N2A | 11428 | 34507;34508;34509 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| N2B | 4931 | 15016;15017;15018 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| Novex-1 | 5056 | 15391;15392;15393 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| Novex-2 | 5123 | 15592;15593;15594 | chr2:178635203;178635202;178635201 | chr2:179499930;179499929;179499928 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/R | rs756260320  |
0.029 | 0.03 | N | 0.525 | 0.15 | 0.101711395817 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| Q/R | rs756260320 |
0.029 | 0.03 | N | 0.525 | 0.15 | 0.101711395817 | gnomAD-4.0.0 | 1.50604E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.88945E-05 | 0 | 1.65744E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2919 | likely_benign | 0.2255 | benign | -0.657 | Destabilizing | 0.016 | N | 0.492 | neutral | None | None | None | None | N |
| Q/C | 0.8561 | likely_pathogenic | 0.8151 | pathogenic | -0.089 | Destabilizing | 0.869 | D | 0.616 | neutral | None | None | None | None | N |
| Q/D | 0.6503 | likely_pathogenic | 0.48 | ambiguous | -0.336 | Destabilizing | 0.016 | N | 0.483 | neutral | None | None | None | None | N |
| Q/E | 0.068 | likely_benign | 0.0598 | benign | -0.215 | Destabilizing | None | N | 0.207 | neutral | N | 0.345485013 | None | None | N |
| Q/F | 0.8126 | likely_pathogenic | 0.7349 | pathogenic | -0.235 | Destabilizing | 0.637 | D | 0.627 | neutral | None | None | None | None | N |
| Q/G | 0.5781 | likely_pathogenic | 0.4561 | ambiguous | -1.018 | Destabilizing | 0.075 | N | 0.563 | neutral | None | None | None | None | N |
| Q/H | 0.5127 | ambiguous | 0.3961 | ambiguous | -0.613 | Destabilizing | 0.303 | N | 0.477 | neutral | N | 0.421034109 | None | None | N |
| Q/I | 0.3889 | ambiguous | 0.2994 | benign | 0.274 | Stabilizing | 0.366 | N | 0.663 | prob.neutral | None | None | None | None | N |
| Q/K | 0.3282 | likely_benign | 0.2043 | benign | -0.38 | Destabilizing | 0.012 | N | 0.502 | neutral | N | 0.414398597 | None | None | N |
| Q/L | 0.2418 | likely_benign | 0.1699 | benign | 0.274 | Stabilizing | 0.058 | N | 0.539 | neutral | N | 0.433416014 | None | None | N |
| Q/M | 0.349 | ambiguous | 0.3083 | benign | 0.448 | Stabilizing | 0.637 | D | 0.473 | neutral | None | None | None | None | N |
| Q/N | 0.4586 | ambiguous | 0.3232 | benign | -0.882 | Destabilizing | 0.075 | N | 0.476 | neutral | None | None | None | None | N |
| Q/P | 0.9422 | likely_pathogenic | 0.8646 | pathogenic | -0.007 | Destabilizing | 0.11 | N | 0.52 | neutral | N | 0.437171695 | None | None | N |
| Q/R | 0.3998 | ambiguous | 0.2794 | benign | -0.297 | Destabilizing | 0.03 | N | 0.525 | neutral | N | 0.414836254 | None | None | N |
| Q/S | 0.3119 | likely_benign | 0.2361 | benign | -1.031 | Destabilizing | 0.016 | N | 0.514 | neutral | None | None | None | None | N |
| Q/T | 0.2265 | likely_benign | 0.1846 | benign | -0.717 | Destabilizing | 0.075 | N | 0.473 | neutral | None | None | None | None | N |
| Q/V | 0.2372 | likely_benign | 0.187 | benign | -0.007 | Destabilizing | 0.075 | N | 0.555 | neutral | None | None | None | None | N |
| Q/W | 0.8906 | likely_pathogenic | 0.8393 | pathogenic | -0.136 | Destabilizing | 0.869 | D | 0.62 | neutral | None | None | None | None | N |
| Q/Y | 0.7254 | likely_pathogenic | 0.6049 | pathogenic | 0.077 | Stabilizing | 0.637 | D | 0.521 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.